Mycotoxin and Role of toxin Binder in Livestock and, poultry production

Dr.Kedar Karki. Vet Officer Central Animal Disease Investigation Laboratory Tripureswor
Introduction Mycotoxicoses, the manifestation of mycotoxin poisoning, has long been appreciated as an acute cause of poor animal performance. It is only recently that chronic, sub clinical mycotoxin load has been appreciated as a cause of poor animal performance and increased disease susceptibility. The adverse effects of mycotoxins are thought to be due to both a direct effect on the animal and indirect by suppression of the immune system. Molds and mycotoxins are widely distributed in nature, occurring whenever there is sufficient organic matter, temperature and water for them to reproduce. Because of the large volume of feedstuffs that must be stored and distributed on dairy farms, considerable opportunity exists for mold growth to appear. Some, if not all, molds can produce a mycotoxin when subjected to stress. These mycotoxins ingested either in large single doses or in small quantities over a long period of time can have adverse effects on the productive capacity, the reproductive efficiency and the health of the animals. Unfortunately, much of what we know about mycotoxins is conjecture, because definitive studies on their effects in dairy cattle are lacking . Therefore, much of this paper must deal with field experience as it relates to the solution of mycotoxicosis. The focus of this paper will be on the practical and scientific aspects of mycotoxicosis. Is there a problem ? In general, it is difficult to make a confirmed diagnosis of mycotoxicosis. There are several general symptoms that may make one suspicious that a mycotoxin problem may exist. Many of these symptoms are general and can be symptomatic of other problems.
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Consumption of dry matter is much less (-2.0 kg or 5lb) or much more (+2.0 kg or 5 lb)than would be predicted for the present production. Less dry matter is generally a symptom of aflatoxion or other serious mycotoxins. More intake than production warrants can indicate problems with DON (deoxynivalenol) or zearalenone. A high incidence of digestive upsets. These upsets can take the form of diarrhea and or rumen stasis ("impactions"). Almost any mycotoxin will at some dosage provoke these symptoms. Presence of a lot of mucous in the manure. This is symptomatic of all mycotoxins, but much more prevalent with aflatoxin or T-2 toxin. Presence of large amounts of mucous is symptomatic or a toxin, although it may not always be a mycotoxin. A high influence of disease associated with depressed immune function, such as unrealism or Pasteurella pneumonia. Presence of a generalized tissue edema. This is often evidenced by swelling in the brisket and hock areas. Cows are very sensitive to any type of impact or insult. Swelling is often in excess of what would be expected. This is associated with mycotoxins of the Fusarium type.

A high rate of abortion or fetal resorption without obvious infectious disease involvement. A total rate of abortion and resorption above 15 percent would be considered high . Again almost all molds provoke abortions. It is not necessary to have mycotoxins to produce abortions. High levels of even benign molds can cause mycototic abortions. However, high resumption rates coupled with short heats or nymphomania may indicate zearalenone contamination. 7. A general unthrifty appearance of the cattle with lower milk production than would be expected. Cows could have rough hair coats, a "sad" appearance and generally a slightly arched back. Calculation of the ration would indicate more milk production and better appearance than is evidenced by the cows. 8. Animals do not respond well to treatment for diseases. None of these manifestations can be considered diagnostic. But when they exist, especially in the absence of more typical explanations, like poor management or presence of infectious disease, the possibility of mycotoxicosis should be explored and steps taken immediately to reduce the potential for mycotoxins to be a problem.
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General Considerations For mold growth to occur, four conditions must exist: (1) there must be an adequate food source; (2) The temperature must be maintained between 12 and 31 (C; (3) there must be sufficient oxygen to allow mold growth; and (4) there must be sufficient moisture, at least in some parts of feed, for mold growth. Thus, if the farmer can control the availability of oxygen and moisture, he can go al long way to prevent mycotoxins from being produced on the farm. Molds produce mycotoxins in response to stress. For example, molds growing on corn, either in the field or in storage, will produce no mycotoxin until subjected to freezing temperatures or until subjected to moisture deprivation. Mycotoxin problems are more pronounced in crops growing under cool, moist conditions and under drought stressed conditions. Unfortunately both of these conditions and under drought stressed conditions. Unfortunately both of these conditions occur annually in large portions of the world. Mycotoxin production will be in direct proportion to the duration of this stress. Conversely, it is possible that feeds heavily contaminated with mold scan be mixed, ground or treated so that obvious mold is not evident. Yet, this feed can be completely contaminated with mycotoxins. Thus, a feed and have molds and still not contain mycotoxins and have mycotoxins without mold. The only way to properly evaluate these situations is the reaction of the cows. Even if mycotoxins are present, it may be difficult to demonstrate their presence or their relative severity. Although there have been about 400 mycotoxins identified, there are probably as many that have not been fully characterized. Also, pure mycotoxin may have little animal impact. However, the same mycotoxin, given at lower dose, but in conjunction with another mycotoxin, may have a devastating effect on the health and productive ability of the animal. Apparently different mycotoxins can potentiate the effect of other mycotoxins. In general, animal symptoms include; poor milk production, poor feed consumption, poor body condition, diarrhea, quantities of mucous in the manure, anestrous, poor reproductive performance, abortion, high disease incidence and general lethargy. However, presence of two or more mycotoxins may completely change the symtomoloty of the mycotoxicosis. Also, many of these are general symptoms and are the symptoms of other toxicosis, parasites, disease,

management or simply poor environmental conditions. May herds where mycotoxins have been a persistent problem have been labeled as "poor managers." Thus, someone with experience and a consistent analytical approach needs to sort out whether the problem is mycotoxins or other factors. At the end of the day, this may be difficult to prove. Normally, we believe that mycotoxins should be considered only after other cause of poor performance have been fully explored. This does not mean that the mycotoxin needs to be demonstrated before melioration takes place. For various reasons, it may be impossible to demonstrate a toxin. Rather , if mycotoxin is suspected, the suspect feed should be removed, or at least the quantities of the suspect feed decreased, and a toxin binder should be added to the ration. Then cow performance should be evaluated. If health and production improve, then one should keep pursuing the avenue of mycotoxins. If the change in cow performance occur, obviously another track should be taken. Mycotoxins tend to accumulate in the liver, causing liver toxicosis. Increases in the liver enzymes, particularly SGOT (serum glutamic acid oxalate transaminase) and LDH (Lactic dehydrogenase), along with increased serum cholesterol levels and decreased whit cell counts without elevated body temperature are considered inclinators of mycotoxins. Immune system depression is another classic symptom of mycotoxicosis. Many of the reproductive and health effects are believed to be the result of the general immune suppression. However, there is also a "mycological abortion" syndrome, where ingestion of molds and mycotoxins directly results in the termination of gestation. Additionally, evidence exists that abortions now identified as Neosporin conium abortions may in fact be potentiated by mycotoxin. In general, mycotoxins are toxic to rumen bacteria, although it is thought that rumen microorganisms detoxify between 80-90% of ingested mycotoxin. The other major site of mycotoxin action tends to be in the intestines, both large and small. Depending on the toxin, malabsorption of nutrients, excessive mucous production, tissue erosion, hemorrhage and tissue necrosis have been reported. This often leads to loss of appetite, severe diarrhea and weight loss. Mycotoxin problems tend to be typical of the farm or herd. Whether this is because of large amounts of inoculums present either in the fields or in the storage structures, or whether there is bad management of the feed and feeding program is not known. However, the author has personally seen herds with apparently excellent feed preservation and feed management that still had highly contaminated feeds. Farms that have a history of mycotoxicosis should add toxin binders as a regular management practice. Again, a word of caution: many of these symptoms are not of themselves diagnostic. Also, not all mycotoxins manifest these symptoms, and combinations of mycotoxins can produce symptoms that are more severs or less pronounced than those listed. A diagnosis of mycotoxicosis is not a panacea. Often, depending on the type of mycotoxin and the degree to which the liver has been damaged, recuperation is slow, or in the case of cows with severely damaged livers, it does not occur every year. Unfortunately, some of theist corn, because it will not pass quality tests for the U.S. market, is price discounted and sold into markets where testing is less stringent. If the price of these grains is significantly below the prevailing market, it should be suspected that some mycotoxin contamination might exist. This grain should be purchased only after it has passed a minimum number of mycotoxin tests. If the feed smells moldy, then reject it as a source of grain for the milking herd . The best advice in dealing with this situation is to know the supplier. Grain dealers will not knowingly sell a bad load of feed to a good client. However, if the purchaser is

buying strictly on price and is dealing on a one-time-only or hit-or-miss basis, the dealer will be more inclined to sell grain based on the lowest purchase price. The situation is largely the same with cottonseed, except that in cottonseed, aflatoxin is by far the greatest danger. Each year both in the U.S. and in Latin American countries, dairy farmers will experience aflatoxin toxicity with some herds due to infected cottonseed. In every case, this will be traced to the cottonseed being stored at too high a humidity or to cottonseed that got rained on after storage. The save advice applies to cottonseed as to corn. Reject obviously contaminated supplies and buy from a known dealer. Testing It has long been established in disease situations that the presence of the disease must be demonstrated before treatment should begin. This is certainly desirable must be demonstrated before treatment should begin. This is certainly desirable in situations where mycotoxins present. There are, however, several caveats that must be applied to mycotoxin testing. While demonstration of absence of mycotoxin is good, demonstration of presence is not necessarily bad. First, virtually all feed contains some mycotoxins at some level. This is a natural situation, and the animal has a natural ability to detoxify some mycotoxin. It is only when mycotoxins reach a critical dose that there are potential problems. For example, 5 ppb (parts per billion) of zearalenone is no is no cause for concern, 50 ppb could be, while 100 ppb (unfortunately, a situation found in many corn silages) is definitely dangerous. Many double inane assay kits used in feed mills and on farms are not calibrated to reflect mycotoxin levels. We must know what the level of contamination is before we can make adequate recommendations. Tests without quantification are useless. 2. As stated above, tests for the mold do not indicate presence of mycotoxin. We must test for mycotoxin in order to demonstrate true toxicity. 3. Sampling of the feed, always crucial, is even more critical in mycotoxin analysis. Silage samples should be taken across the entire face of the bunk, not just on the edges where there are sure to be higher loads of mycotoxin and not just at the center, where there should be none. If a grain is suspected, samples must be taken in various places in the bin. A TMR sample is excellent in this case, but again take samples from the beginning, middle and end of the batch. These samples need to be taken over several days and then combined. 4. Absence of one mycotoxin does not mean absence of all mycotoxins. For example, a feed may be free of aflatoxin and lace with zearalenone. Or it could be free of both aflatoxin and zearalenone and be contaminated with T-2 5. Demonstration of one mycotoxin does not mean there are no others. Often laboratories test for aflatoxin first. If this is found, they stop. it is very possible that feeds contaminated by one mycotoxin may have several mycotoxins, Thus, testing should not stop with the confirmation of one mycotoxin. 6. There will be times when no mycotoxin can be demonstrated, but when steps are taken to reduce mycotoxin effects, a positive result is produced in the cows, Unfortunately, we do not know enough about mycotoxins to be able to identify each one. Known mycotoxins
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The following is a list of the most well described mycotoxins, their origin, and their approximate safe levels of inclusion as ppm of ppb per total dry matter, This list is by no means exhaustive, nor can the levels of mycotoxin assumed to be safe be tolerated by cattle under all circumstances. It is well known that lower levels of several mycotoxins have a greater effect than one mycotoxin in high dosage. Also the safe levels of mycotoxin listed below are at acute intakes. Feeding of lower levels for prolonged periods of time may result in the same or more severe symptoms 1.Aflatoxin is the mycotoxin that is best recognized and vest characterized. It is produced by molds of the aspergillums species and is a potent carcinogen. This is the reason aflatoxin levels are regulated in raw milk in the United States, Symptoms include: decreased production, weight loss, high lover enzymes, loss of liver function, abortion and ultimately death. Although aflatoxin is perhaps the most dangerous of the mycotoxins, it really does little practical damage. This is because its effects are severs and dramatic, which makes the change to aflatoxin contaminated feeds noticeable. It is quickly associated with feed changes, and the offending feed can either be reduced in quantity or removed. Also, feed companies readily appreciate the damage that aflatoxin can do and regularly screen for its presence. Thus, aflatoxin is really not the severe problem that it could be if left unscreened. If lever damage is not severs, animals usually recover in 4-10 days after the offending feed has been removed. On a practical basis, 20 ppb can probably be well tolerated by mature milking cows, but only about 10 ppb in growing cattle and 4 ppb for calves, For chronic feeding these kevels should be reduced by one half. 2. Deoxynivalenol (DON) is produced by molds of the Fusarium species. Much of the data in dairy cattle concerning the effects of DON have caused no noticeable problems: however, lower doses of DON below 500 ppb are probably safe for consumption by dairy cattle. 3. Zearalenone is a mycotoxin with estrogenic activity which is also produced by moles of the Fusarium species, Lowered milk production, abortion, short heat cycles, nymphomania and feminization of bulls have been reported when feeding zearalenone infected silages, Zearalenol is compound similar to zearaleone but is reported to provoke 5-10 times the estrogen response. Levels of zearalenone below 250 ppb are probably safe to feed adult dairy cattle if no other molds are contaminating the feed. 4. T-2 toxin (one of the trichothecence) is also produced by several molds of the Fusarium species. T-2 is found not only in corn silage but also in some haulages. Symptoms in cattle include lowered milk production, diarrhea, hemorrhagic bowel, sterility, and lesion in the intestine, ovaries and uterus, immune function is severely depressed. Consumption of large quantities can cause acute death. Consumption of greater than 100 ppb are probably dangerous for cattle. Diacetoxyscirpenol (DAS) is a closely related compound that produces many of the same effects. Fifty ppb is the safe suggested limit for this toxin. 5. Fumonisin has been reported relatively recently, and the effects are still relatively unknown. It has been implicated in liver and kidney damage, decreased immune function and high mortality rates in cattle. It is tumorgenic in swine and horses, but this has not been demonstrated in cattle. Fumonisin is thought to potentiate the toxicity of other trichothecene toxins. Safe levels have been estimated to be below 50,000 ppb. Five thousand ppb is the maximum safe level for horses. 6. Ergot is a mold that infects the flowering portion of many grins and grasses. Abortion storms and lowered fertility are associated with consumption of ergot infected feeds, Although fanatic in its effects, ergot is probably not an industry wide problem. Cattle fed less than 0.5% (5000ppm) of dry matter as ergot showed no adverse reproductive effects, but cattle fed at 1% (10,000ppm) had increased abortion rates with calves that were born alive being weak and debilitated.

7. Ochratoxin is a mycotoxin produced almost always on grains and almost always as a result of poor storage conditions by molds of the Penicllium family and by Aspergillus coracles. Controlled studies in dairy animals are lacking, although cattle fed Ochratoxin contaminated feed had enlarged livers and kidneys at slaughter. Safe levels are assumed to be less than 10,000ppb. While many other mycotoxins that infect feed are known, they are usually a problem in areas of the world other than the Americas. Conclusion Mycotoxins, especially those produced by Fusarium species, may result in great losses in productivity. Although aflatoxin is widely recognized as a potent mycotoxin, It is probable not the problem that either feed dealers of veterinarians believe it to be. All obviously moldy or damaged feed should be avoided. Silages are one of the largest sources of mycotoxin contamination, Silages need to be well managed from the time of ensiling through the feed out process, Silages should be treated with a mold inhibitor in situations where at least 15 cm of silage cannot be removed from the face. A mycotoxin binder should be added to the feed mix whenever moldy fed is being utilized or whenever mycotoxin are suspected. Mixing should occur for sufficient time to insure completes distribution of both the suspect contaminated feed and the mycotoxin binder. The use of Anti-Degnala –Liquor has also been found useful in such condition. Lastly, be ever vigilant. Mycotoxins, even in low doses but fed continually for long periods of time, reduce productivity and reproduction while increasing morbidity. Constant monitoring and geed on-farm feed management, including good management and inclusion of mold inhibitors and binders, will reduce the economic impact of molds and mycotoxins. Personal Observations and practice Regarding mycotoxin Binders I have been involved as a dairy consultant to both farmers and feed dealers in Nepal. In each of these areas I have found evidence of what we believed to be mycotoxicosis, Mycotoxins seem to be a more consistent problem in areas where high levels of by-product feeds are used in concentrates and/flock have been mismanaged. The diagnosis of mycotoxicosis has been complicated by the fact that in many areas, identification of mycotoxins is not always possible. This is for various reasons, including inability of laboratories to provide adequate testing. In a few instances even when there was confirmed mycotoxin, particularly in cases of zearalenone or T-2 toxin, and a "mycotoxin binder" was added, the recovery of the herd has proven to be intractable. Cocktail products generally include several types of clays as well as vitamins and other minerals, Chemically, these binders are all clays and have more or less the same chemical composition. However, morphology, purity and ability to form chemical bonds with mycotoxins differ widely among both the types of these clays and their manufacturing process. A part of this antidegnala liquors has also been found use full My opinion about which type of clays perform better is based solely on field experience but they are supported by in vitro binding experiments. We have found the clays that identify themselves as phyllosilicates, a subclass of aluminosilicates, are definitely superior to the others especially when treating mycotoxins of the Fusarium species. In our opinion the absolute best of these products is a phyllosilicates of Mexican origin which is known by the trade name of H.S.C.A.S. It used this product at dosages of 150-250g per head per day in several difficulty situations involving fusariums with outstanding results. In any case, a binder selected for use should have research data that indicates, both in vitro and in vivo, that it binds mycotoxins and keeps the mycotoxin sequestered throughout the digestive

process. Additionally, there should be data indicating if there is binding of minerals and/or vitamins. With this information in hand, one can determine the level of extra supplementation that might be necessary. In many cases, when reproductive parameters are sub par or when there is a high-level of digestive upsets than I consider normal, I recommend mycotoxin binders of the alumonosilicate type as a prophylactic. While the economic benefits of this action are hard to measure, reproductive records definitely show improvement. Generally, records also show improved animal health. More reading and Reference Material
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Apple Baum, R.S., R.E Brackett, D.W. Wiseman and E.H. Marth. Aflatoxin: Toxicity to dairy cattle and occurrence in milk and milk products-a review. J. of Food Protection. 45:752, 1982. Christensen, C.M., C.J. Mirocha and R.A. Meronuck. Molds and mycotoxins in feeds. Extension Service, University of Minnesota. 1988. Diekman, M.A. and M.L. Green. Mycotoxins and Reproduction in Domestic Livestock. J. Anim. Sci. 70:1615, 1992. Jacovsen, B.J., K.I. Bown, R.A. Shelby, U.L. Diener, B.W.Kmppaonen and J. Floya. Mycotoxins and mycotoxicoses. Alavama Copertive Extension service, 1992. Jones, F.T., M.B. Genter, W.M. Hagler, J.A. Hansen, B.A. Mowrey, M.H. Moore and L.W. Whitlow. Understanding and coping with effects of mycotoxins in livestock feed and forage. North Carolina Cooperative Extension service, 1994. Patton, R.A. and H.F. Bucholtz. Molds and mycotoxins in dairy cattle feed. Extension Service, Michigan state University, 1986. Pier, A.C., J.L. Richard and S.J. Cysewski. Implications of mycotoxins in animal disease, JAVMA 176:719, 1980. Smith, T.K. Recent advances in the understanding of Fusarium trichothecene mycotoxicoses. J. Anim. Sci. 70: 3989 , 1992. B.S. in Dairy Production, Penn State University, 1968. Karki Kedar. assessment Immunogenic Properties and Pathogenesis of F. graminearum and treatment. (2003 M.V.St. Thesis C.LS.U -Philippines